One size does not fit all: micro- meso and macrobleeds in cerebral amyloid angiopathy.

ABSTRACT

INTRODUCTION: MRI rating criteria for small vessel disease markers include definitions for microbleeds and macrobleeds, but do not account for small (<10 mm) hemorrhages with a cystic cavity and/or irregular shape. Such hemorrhages, however, are often present in patients with cerebral amyloid angiopathy (CAA). In this study we aim to investigate the frequency, diameter and volume distribution of these hemorrhages (which we called mesobleeds) in patients with CAA. METHODS: We selected participants with Dutch-type hereditary (D-CAA) and sporadic (s)CAA and scored microbleeds, mesobleeds and macrobleeds on 3T susceptibility weighted images (SWI) MRI. Hemorrhage diameter and volume were calculated in a subset of participants using a semi-automatic tool, their distribution was evaluated on a logarithmic scale. RESULTS: We included 25 participants with D-CAA (mean age 56y) and 25 with sCAA (mean age 73y). In total 11007 microbleeds, 602 mesobleeds and 195 macrobleeds were observed. Eighty-two percent of participants had ≥1 mesobleed. Hemorrhage diameter and volume were calculated in four participants with 272 microbleeds (median diameter 1.52mm, volume 0.004ml), 84 mesobleeds (median diameter 5.61mm, volume 0.06ml) and 37 macrobleeds (median diameter 19.58mm, volume 1.33ml). Mesobleed diameter and volume were larger than microbleeds (optimal cut-off 0.02ml) but showed overlap with macrobleeds. CONCLUSION: Hemorrhages <10mm with an irregular shape and/or cystic cavity are frequently found in participants with CAA and have a distinct diameter and volume distribution. We propose to name these hemorrhages mesobleeds and to rate them separately from micro- and macrobleeds. Future research is necessary to investigate their pathophysiology and prognostic value.